Influence of Glucocorticoids on Cellular Senescence Hallmarks in Osteoarthritic Fibroblast-like Synoviocytes

Osteoarthritis (OA) is recognized as being a cellular senescence-linked disease. Intra-articular injections of glucocorticoids (GC) are frequently used in knee OA to treat synovial effusion but face controversies about toxicity. We investigated the influence of GC on cellular senescence hallmarks an...

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Autores principales: Olivier Malaise, Geneviève Paulissen, Céline Deroyer, Federica Ciregia, Christophe Poulet, Sophie Neuville, Zelda Plener, Christophe Daniel, Philippe Gillet, Chantal Lechanteur, Jean-Marc Brondello, Dominique de Seny, Michel Malaise
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:34cc2a99573a4e5a867fd07d7f611b832021-11-25T18:01:49ZInfluence of Glucocorticoids on Cellular Senescence Hallmarks in Osteoarthritic Fibroblast-like Synoviocytes10.3390/jcm102253312077-0383https://doaj.org/article/34cc2a99573a4e5a867fd07d7f611b832021-11-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/22/5331https://doaj.org/toc/2077-0383Osteoarthritis (OA) is recognized as being a cellular senescence-linked disease. Intra-articular injections of glucocorticoids (GC) are frequently used in knee OA to treat synovial effusion but face controversies about toxicity. We investigated the influence of GC on cellular senescence hallmarks and senescence induction in fibroblast-like synoviocytes (FLS) from OA patients and mesenchymal stem cells (MSC). Methods: Cellular senescence was assessed via the proliferation rate, β-galactosidase staining, DNA damage and CKI expression (p21, p16<sup>INK4A</sup>). Experimental senescence was induced by irradiation. Results: The GC prednisolone did not induce an apparent senescence phenotype in FLS, with even higher proliferation, no accumulation of β-galactosidase-positive cells nor DNA damage and reduction in p21mRNA, only showing the enhancement of p16<sup>INK4A</sup>. Prednisolone did not modify experimental senescence induction in FLS, with no modulation of any senescence parameters. Moreover, prednisolone did not induce a senescence phenotype in MSC: despite high β-galactosidase-positive cells, no reduction in proliferation, no DNA damage and no CKI enhancement was observed. Conclusions: We provide reassuring in vitro data about the use of GC regarding cellular senescence involvement in OA: the GC prednisolone did not induce a senescent phenotype in OA FLS (the proliferation ratio was even higher) and in MSC and did not worsen cellular senescence establishment.Olivier MalaiseGeneviève PaulissenCéline DeroyerFederica CiregiaChristophe PouletSophie NeuvilleZelda PlenerChristophe DanielPhilippe GilletChantal LechanteurJean-Marc BrondelloDominique de SenyMichel MalaiseMDPI AGarticleosteoarthritissynovial membraneclinical studiesMedicineRENJournal of Clinical Medicine, Vol 10, Iss 5331, p 5331 (2021)
institution DOAJ
collection DOAJ
language EN
topic osteoarthritis
synovial membrane
clinical studies
Medicine
R
spellingShingle osteoarthritis
synovial membrane
clinical studies
Medicine
R
Olivier Malaise
Geneviève Paulissen
Céline Deroyer
Federica Ciregia
Christophe Poulet
Sophie Neuville
Zelda Plener
Christophe Daniel
Philippe Gillet
Chantal Lechanteur
Jean-Marc Brondello
Dominique de Seny
Michel Malaise
Influence of Glucocorticoids on Cellular Senescence Hallmarks in Osteoarthritic Fibroblast-like Synoviocytes
description Osteoarthritis (OA) is recognized as being a cellular senescence-linked disease. Intra-articular injections of glucocorticoids (GC) are frequently used in knee OA to treat synovial effusion but face controversies about toxicity. We investigated the influence of GC on cellular senescence hallmarks and senescence induction in fibroblast-like synoviocytes (FLS) from OA patients and mesenchymal stem cells (MSC). Methods: Cellular senescence was assessed via the proliferation rate, β-galactosidase staining, DNA damage and CKI expression (p21, p16<sup>INK4A</sup>). Experimental senescence was induced by irradiation. Results: The GC prednisolone did not induce an apparent senescence phenotype in FLS, with even higher proliferation, no accumulation of β-galactosidase-positive cells nor DNA damage and reduction in p21mRNA, only showing the enhancement of p16<sup>INK4A</sup>. Prednisolone did not modify experimental senescence induction in FLS, with no modulation of any senescence parameters. Moreover, prednisolone did not induce a senescence phenotype in MSC: despite high β-galactosidase-positive cells, no reduction in proliferation, no DNA damage and no CKI enhancement was observed. Conclusions: We provide reassuring in vitro data about the use of GC regarding cellular senescence involvement in OA: the GC prednisolone did not induce a senescent phenotype in OA FLS (the proliferation ratio was even higher) and in MSC and did not worsen cellular senescence establishment.
format article
author Olivier Malaise
Geneviève Paulissen
Céline Deroyer
Federica Ciregia
Christophe Poulet
Sophie Neuville
Zelda Plener
Christophe Daniel
Philippe Gillet
Chantal Lechanteur
Jean-Marc Brondello
Dominique de Seny
Michel Malaise
author_facet Olivier Malaise
Geneviève Paulissen
Céline Deroyer
Federica Ciregia
Christophe Poulet
Sophie Neuville
Zelda Plener
Christophe Daniel
Philippe Gillet
Chantal Lechanteur
Jean-Marc Brondello
Dominique de Seny
Michel Malaise
author_sort Olivier Malaise
title Influence of Glucocorticoids on Cellular Senescence Hallmarks in Osteoarthritic Fibroblast-like Synoviocytes
title_short Influence of Glucocorticoids on Cellular Senescence Hallmarks in Osteoarthritic Fibroblast-like Synoviocytes
title_full Influence of Glucocorticoids on Cellular Senescence Hallmarks in Osteoarthritic Fibroblast-like Synoviocytes
title_fullStr Influence of Glucocorticoids on Cellular Senescence Hallmarks in Osteoarthritic Fibroblast-like Synoviocytes
title_full_unstemmed Influence of Glucocorticoids on Cellular Senescence Hallmarks in Osteoarthritic Fibroblast-like Synoviocytes
title_sort influence of glucocorticoids on cellular senescence hallmarks in osteoarthritic fibroblast-like synoviocytes
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/34cc2a99573a4e5a867fd07d7f611b83
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